Prospective Clinical Sequencing of Adult Glioma.

Malignant gliomas are a group of intracranial cancers associated with disproportionately high mortality and morbidity. Here, we report ultradeep targeted sequencing of a prospective cohort of 237 tumors from 234 patients consisting of both glioblastoma (GBM) and lower-grade glioma (LGG) using our customized gene panels. We identified 2,485 somatic mutations, including single-nucleotide substitutions and small indels, using a validated in-house protocol.

Megabase Length Hypermutation Accompanies Human Structural Variation at 17p11.2.

DNA rearrangements resulting in human genome structural variants (SVs) are caused by diverse mutational mechanisms. We used long- and short-read sequencing technologies to investigate end products of de novo chromosome 17p11.2 rearrangements and query the molecular mechanisms underlying both recurrent and non-recurrent events.

Comparison of different functional prediction scores using a gene-based permutation model for identifying cancer driver genes.

Background: Identifying cancer driver genes (CDG) is a crucial step in cancer genomic toward the advancement of precision medicine. However, driver gene discovery is a very challenging task because we are not only dealing with huge amount of data; but we are also faced with the complexity of the disease including the heterogeneity of background somatic mutation rate in each cancer patient. It is generally accepted that CDG harbor variants conferring growth advantage in the malignant cell and they are positively selected, which are critical to cancer development; whereas, non-driver genes harbor random mutations with no functional consequence on cancer.

In-utero cold stress causes elevation of blood pressure via impaired vascular dopamine D receptor in offspring.

Environmental cold stress is an important factor that leads to hypertension. The role and the mechanisms of in-utero cold stress in hypertension in adult offspring remain unknown. The pregnant rats were housed in cold (4°C) rooms from 14 to 21 days of gestation for prenatal cold exposure.

Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas.

Importance: Shared gene variants in benign-malignant process pairs, such as BRAF mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships.

Objective: To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing.

Hypervirulent group A Streptococcus emergence in an acaspular background is associated with marked remodeling of the bacterial cell surface.

Inactivating mutations in the control of virulence two-component regulatory system (covRS) often account for the hypervirulent phenotype in severe, invasive group A streptococcal (GAS) infections. As CovR represses production of the anti-phagocytic hyaluronic acid capsule, high level capsule production is generally considered critical to the hypervirulent phenotype induced by CovRS inactivation. There have recently been large outbreaks of GAS strains lacking capsule, but there are currently no data on the virulence of covRS-mutated, acapsular strains in vivo.

Distinct Biological Types of Ocular Adnexal Sebaceous Carcinoma: HPV-Driven and Virus-Negative Tumors Arise through Nonoverlapping Molecular-Genetic Alterations.

Purpose: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies.

Experimental Design: We present next-generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from eight OA sebaceous carcinomas from 29 patients.

Combining accurate tumor genome simulation with crowdsourcing to benchmark somatic structural variant detection.

Background: The phenotypes of cancer cells are driven in part by somatic structural variants. Structural variants can initiate tumors, enhance their aggressiveness, and provide unique therapeutic opportunities. Whole-genome sequencing of tumors can allow exhaustive identification of the specific structural variants present in an individual cancer, facilitating both clinical diagnostics and the discovery of novel mutagenic mechanisms.

[Patent Traditional Chinese Medicine for idiopathic male infertility: A bibliometrical study].

Objective: To survey the current status of clinical studies on patent Traditional Chinese Medicine (TCM) for idiopathic male infertility in China.

Methods: Using the keywords "oligospermia", "azoospermia", "asthenozoospermia", "infertility" and "sperm", we searched China National Knowledge Internet (CNKI), Wanfang Database and SinoMed for randomized clinical trials (RCT), cohort studies, case-control studies and case series studies focusing on the treatment of male idiopathic infertility using TCM from January 2001 to May 2017. Two individual reviewers screened the literature, extracted the information separately, recorded the titles, authors, related institutions and regions, journals and years of publication, medication studied, and outcomes.

Individualized Medication of Voriconazole: A Practice Guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

Background: Voriconazole (VRZ) is a second-generation triazole antifungal agent with broad-spectrum activity. It is available in both intravenous and oral formulations, and is primarily indicated for treating invasive aspergillosis. The most commonly used dose for adults is 4 mg/kg or 200 mg twice daily.

LncRNA-AK012226 Is Involved in Fat Accumulation in db/db Mice Fatty Liver and Non-alcoholic Fatty Liver Disease Cell Model.

Instances of obesity and related metabolic abnormalities are increasing across the world. Non-alcoholic fatty liver disease (NAFLD) is a common disorder in obese people and is becoming the leading cause of hepatocellular carcinoma. Recently, long non-coding RNAs (lncRNAs) have been proven to play remarkable roles in numerous biological processes and human diseases, including NAFLD.

Depth-driven variable-frequency sinusoidal fringe pattern for accuracy improvement in fringe projection profilometry.

Sinusoidal fringe pattern is widely used in optical profilometry; however, the traditional constant-frequency sinusoidal fringe pattern reduces 3D measurement accuracy in the defocus region. To this end, this paper presents a variable-frequency sinusoidal fringe pattern method that is optimized by the measurement depth. The proposed method improves the pixel matching accuracy and thus increases measurement accuracy.

Structural Variant Breakpoint Detection with novoBreak.

Structural variations (SVs) are an important type of genomic variants and always play a critical role for cancer development and progression. In the cancer genomics era, detecting structural variations from short sequencing data is still challenging. We developed a novel algorithm, novoBreak (Chong et al.

Survival Outcomes by Mutation Status in Metastatic Breast Cancer.

Purpose: We sought to determine the significant genomic alterations in patients with metastatic breast cancer (MBC), and survival outcomes in common genotypes.

Patients And Methods: High-depth next generation sequencing was performed for 202 genes in tumor and normal DNA from 257 patients with MBC, including 165 patients with ER/PR+ HER2- (hormone receptor positive, HR+ positive), 32 patients with HER2+ and 60 patients with triple negative (ER/PR/HER2-) cancer. Kaplan Meier survival analysis was performed in our discovery set, in breast cancer patients analyzed in The Cancer Genome Atlas, and in a separate cohort of 98 patients with MBC who underwent clinical genomic testing.

In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer.

Genetic aberrations driving pro-oncogenic and pro-metastatic activity remain an elusive target in the quest of precision oncology. To identify such drivers, we use an animal model of KRAS-mutant lung adenocarcinoma to perform an in vivo functional screen of 217 genetic aberrations selected from lung cancer genomics datasets. We identify 28 genes whose expression promoted tumor metastasis to the lung in mice.

Irisin Protects Heart Against Ischemia-Reperfusion Injury Through a SOD2-Dependent Mitochondria Mechanism.

Irisin, a muscle-origin protein derived from the extracellular domain of the fibronectin domain-containing 5 protein (FNDC5), has been shown to modulate mitochondria welfare through paracrine action. Here, we test the hypothesis that irisin contributes to cardioprotection after myocardial infarction by preserving mitochondrial function in cardiomyocytes. Animal model studies show that intravenous administration of exogenous irisin produces dose-dependent protection against ischemia/reperfusion (I/R)-induced injury to the heart as reflected by the improvement of left ventricular ejection fraction and the reduction in serum level of cTnI (n = 15, P < 0.

Metachronous Medulloblastoma in a Child With Successfully Treated Neuroblastoma: Case Report and Novel Findings of DNA Sequencing.

Metachronous neoplasms have rarely been reported in patients with neuroblastoma. This report presents the clinical case of a 23-month-old child who was diagnosed with an anaplastic medulloblastoma 5 months after completing treatment for stage IV neuroblastoma. The patient was treated with complete surgical resection and adjuvant chemoradiation followed by maintenance chemotherapy at an outside institution and came to our institution for further management.

GPU based parallel acceleration for fast C-arm cone-beam CT reconstruction.

Background: With the introduction of Flat Panel Detector technology, cone-beam CT (CBCT) has become a novel image modality, and widely applied in clinical practices. C-arm mounted CBCT has shown extra suitability in image guided interventional surgeries. During practice, how to acquire high resolution and high quality 3D images with the real time requirement of clinical applications remain challenging.

Cancer driver mutation prediction through Bayesian integration of multi-omic data.

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels.

Targeted next generation sequencing of well-differentiated/dedifferentiated liposarcoma reveals novel gene amplifications and mutations.

Well-differentiated/dedifferentiated liposarcoma is a common soft tissue sarcoma with approximately 1500 new cases per year. Surgery is the mainstay of treatment but recurrences are frequent and systemic options are limited. 'Tumor genotyping' is becoming more common in clinical practice as it offers the hope of personalized targeted therapy.

Sevoflurane-induced memory impairment in the postnatal developing mouse brain.

The aim of the present study was to confirm that sevoflurane induces memory impairment in the postnatal developing mouse brain and determine its mechanism of action. C57BL/6 mice 7 days old were randomly assigned into a 2.6% sevoflurane (n=68), a 1.

Untying the gordion knot of targeting MET in cancer.

Despite compelling evidence backing the crucial role of a dysregulated MET axis in cancer and a myriad of agents targeting this pathway in active clinical development, the therapeutic value of MET inhibition in cancer oncology remains to be established. Although a series of disappointing clinical trials, at first, lessened fervor for targeting this pathway, investigations continue unabated with a number of novel active compounds entering clinical trials. Suboptimal designs which lacked biomarker selection have been the main reason for these early failures and this has stimulated a more biomarker enriched approach lately.

The Immune Landscape of Cancer.

We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers.